Servomotor-Linked Articulated Versatile End Effector (SLAVE2)

A strategy is presented for the design and construction of a large master/slave-controlled, five-finger robotic hand. Each of the five fingers will possess four independent axes each driven by a brushless DC servomotor and, thus, four degrees-of-freedom. It is proposed that commercially available components be utilized as much as possible to fabricate a working laboratory model of the device with an anticipated overall length of approximately three feet (0.9 m). The fingers are to be designed to accommodate proximity, tactile, or force/torque sensors imbedded in their structure. In order to provide for the simultaneous control of the operator wears a specially instrumented glove which produces control signals corresponding to the finger configuration and which is capable of conveying sensor feedback signals to the operator. Two dexterous hand master devices are currently commercially available for this application with both undergoing continuing development

Serological Profiling of a Candida albicans Protein Microarray Reveals Permanent Host-Pathogen Interplay and Stage-Specific Responses during Candidemia

Candida albicans in the immunocompetent host is a benign member of the human microbiota. Though, when host physiology is disrupted, this commensal-host interaction can degenerate and lead to an opportunistic infection. Relatively little is known regarding the dynamics of C. albicans colonization and pathogenesis. We developed a C. albicans cell surface protein microarray to profile the immunoglobulin G response during commensal colonization and candidemia. The antibody response from the sera of patients with candidemia and our negative control groups indicate that the immunocompetent host exists in permanent host-pathogen interplay with commensal C. albicans. This report also identifies cell surface antigens that are specific to different phases (i.e. acute, early and mid convalescence) of candidemia. We identified a set of thirteen cell surface antigens capable of distinguishing acute candidemia from healthy individuals and uninfected hospital patients with commensal colonization. Interestingly, a large proportion of these cell surface antigens are involved in either oxidative stress or drug resistance. In addition, we identified 33 antigenic proteins that are enriched in convalescent sera of the candidemia patients. Intriguingly, we found within this subset an increase in antigens associated with heme-associated iron acquisition. These findings have important implications for the mechanisms of C. albicans colonization as well as the development of systemic infection

Prospective Evaluation of Galactomannan and (1→3) β-d-Glucan Assays as Diagnostic Tools for Invasive Fungal Disease in Children, Adolescents, and Young Adults With Acute Myeloid Leukemia Receiving Fungal Prophylaxis.

BackgroundPatients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis.MethodsTwice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC).ResultsAmong 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1-43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%.ConclusionsThe GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged

Worldwide, mortality risk is high soon after initiation of hemodialysis.

Mortality rates for maintenance hemodialysis patients are much higher than the general population and are even greater soon after starting dialysis. Here we analyzed mortality patterns in 86,886 patients in 11 countries focusing on the early dialysis period using data from the Dialysis Outcomes and Practice Patterns Study, a prospective cohort study of in-center hemodialysis. The primary outcome was all-cause mortality, using time-dependent Cox regression, stratified by study phase adjusted for age, sex, race, and diabetes. The main predictor was time since dialysis start as divided into early (up to 120 days), intermediate (121-365 days), and late (over 365 days) periods. Mortality rates (deaths/100 patient-years) were 26.7 (95% confidence intervals 25.6-27.9), 16.9 (16.2-17.6), and 13.7 (13.5-14.0) in the early, intermediate, and late periods, respectively. In each country, mortality was higher in the early compared to the intermediate period, with a range of adjusted mortality ratios from 3.10 (2.22-4.32) in Japan to 1.15 (0.87-1.53) in the United Kingdom. Adjusted mortality rates were similar for intermediate and late periods. The ratio of elevated mortality rates in the early to the intermediate period increased with age. Within each period, mortality was higher in the United States than in most other countries. Thus, internationally, the early hemodialysis period is a high-risk time for all countries studied, with substantial differences in mortality between countries. Efforts to improve outcomes should focus on the transition period and the first few months of dialysis

Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis

Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from transplantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]:85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability

Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning

Risks of secondary solid cancers among allogeneic hematopoietic cell transplant (HCT) recipients who receive conditioning without total body irradiation are not well known. We evaluated the incidence and risk factors for solid cancers after HCT using high-dose busulfan-cyclophosphamide conditioning in 4318 recipients of first allogeneic HCT for acute myeloid leukemia in first complete remission (N = 1742) and chronic myeloid leukemia in first chronic phase (N = 2576). Our cohort represented 22 041 person-years at risk. Sixty-six solid cancers were reported at a median of 6 years after HCT. The cumulative-incidence of solid cancers at 5 and 10 years after HCT was 0.6% and 1.2% among acute myeloid leukemia and 0.9% and 2.4% among chronic myeloid leukemia patients. In comparison to general population incidence rates, HCT recipients had 1.4× higher than expected rate of invasive solid cancers (95% confidence interval, 1.08-1.79, P = .01). Significantly elevated risks were observed for tumors of the oral cavity, esophagus, lung, soft tissue, and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers, and especially cancers of the oral cavity. Recipients of allogeneic HCT using busulfan-cyclophosphamide conditioning are at risk for developing solid cancers. Their incidence continues to increase with time, and lifelong cancer surveillance is warranted in this population

Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation

Copyright © 2002 by The American Society of Hematology.Life-threatening complications such as graft versus host disease and infection remain major barriers to the success of allogeneic hemopoietic stem cell transplantation (SCT). While pretransplantation conditioning and posttransplantation immunosuppression are important risk factors for infection, the reasons that similarly immunosuppressed transplant recipients show marked variation in frequency of infection after allogeneic SCT are unclear. Mannose-binding lectin (MBL) deficiency is a risk factor for infection in other situations where immunity is compromised. We investigated associations between MBL2 gene polymorphisms and risk of major infection following allogeneic SCT. Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data including survival, days of fever, graft versus host disease incidence and severity, and infection were collected by case note review. Five single-nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase chain reaction and sequence-specific primers. MBL2 coding mutations were associated with an increased risk of major infection following transplantation. This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with major infection. The high-producing haplotype HYA was associated with a markedly reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR 0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently associated with infection in multivariate analysis. These results suggest that MBL2 genotype influences the risk of infection following allogeneic SCT and that both donor and recipient MBL2 genotype are important. These findings raise the possibility that MBL replacement therapy may be useful following transplantation.Charles G. Mullighan, Sue Heatley, Kathleen Doherty, Ferenc Szabo, Andrew Grigg, Timothy P. Hughes, Anthony P. Schwarer, Jeff Szer, Brian D. Tait, L. Bik To, and Peter G. Bard